Disorder of immune Disorder of immune systemsystem

Yeong-Wook Song, MDYeong-Wook Song, MD

Division of RheumatologyDivision of Rheumatology

Seoul National UniversitySeoul National University

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Objectives1 Define the terms infection, pathogen, and

antigen, tolerance, autoimmunity, rheumatic disease.

2 List and describe mechanism of the nonspecific and specific body defense mechanisms.

3 Explain the signs and causes of inflammation.

4 Define B cells and T cells and describe their locations and functions.

5 Explain the importance of MHC proteins.

The Immune SystemThe Immune System

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Objectives (cont.)6 List the different types of T cells and describe

their functions.7 List the different types of antibodies and

explain how they differ and how they fight infection.

8 Define complement and give its functions.9 Explain the difference between innate and

adaptive immunity.10 Describe the signs and symptoms of common

immune disorders (rheumatoid arthritis, lupus, ankylosing spondylitis scleroderma, myositis).

The Immune SystemThe Immune System

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What does the immune system do?

• Normal (physiologic) functions: – Immunity = protection against infection – Defense against some tumors

• Roles in disease: – Cause of many immunological diseases (allergies, autoimmune

diseases) – Suspected role in many diseases thought to be non-immune

(atherosclerosis, Alzheimer’s disease, type 2 diabetes)

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Innate immunity: always present (ready to attack); many pathogenic microbes have evolved to resist innate immunityAdaptive immunity: stimulated by exposure to microbe; more potent

Innate and adaptive immunity

Abbas, Lichtman and Pillai. Cellular and Molecular Immunology, 7th edition, 2011 c Elsevier

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Cells of the immune system

• Lymphocytes: the cells of adaptive immunity; recognize antigens and develop (differentiate) into cells that perform the defense functions

• Antigen-presenting cells: cells that capture antigens and display them to lymphocytes

• Effector cells: leukocytes (white blood cells) that eliminate microbes (the “effect” of the immune response); may be lymphocytes, but are often other leukocytes

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Classes of lymphocytes

Excluding NK cells and other innate lymphoid cells Abbas, Lichtman and Pillai. Cellular and Molecular Immunology, 7th edition, 2011 c Elsevier

Lymphocytes with highly specific and diverse antigen receptors develop prior to exposure to antigens

Lymphocyte diversity and clonal selectionGeneration of mature lymphocytes with

many different antigen receptors

Naïve lymphocytes circulate through lymphoid organs

Specific lymphocytes recognize antigens

Lymphocytes are activated to proliferate and to differentiate into

effector cells

Lymphocyteprecursor

Antigen XAntigen Y

Anti-Yantibody

Anti-Xantibody

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Adaptive immune responses

Stages in the life history of lymphocytes

Proliferation: expands number of antigen-specific cells Differentiation: converts lymphocytes into effective defenders

The immune system can cause disease

• Excessive, uncontrolled responses against infectious pathogens (collateral damage)

• Inappropriate responses against self antigens may cause injury to normal tissues, resulting in disease

• Fundamental defect is failure of control mechanisms in the immune system

The significance of recent advances

Provides a solid foundation of basic principles

Improved understanding of disease mechanisms

Development of novel therapies

Appreciation of the role of the immune system in non-immune diseases

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InflammationInflammation

Signs: Signs: RednessRedness HeatHeat SwellingSwelling PainPain

Signs: Signs: RednessRedness HeatHeat SwellingSwelling PainPain

Causes:Causes: Injured or

infected with a pathogen, inflammation can result

Causes:Causes: Injured or

infected with a pathogen, inflammation can result

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Major Immune Major Immune System DisordersSystem DisordersDiseases and disorders that Diseases and disorders that challenge the immune system: challenge the immune system: (the following are the most (the following are the most significant)significant) HIV/AIDSHIV/AIDS InfectionsInfections Autoimmune diseaseAutoimmune disease CancerCancer AllergiesAllergies

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Acquired Immune Acquired Immune Deficiency Syndrome Deficiency Syndrome (AIDS)(AIDS)

Caused by human Caused by human immunodeficiency immunodeficiency virus (HIV) virus (HIV) infection infection

Most common routes Most common routes of transmission are of transmission are through sexual through sexual contact, blood, or contact, blood, or from mother to from mother to child during child during pregnancy or pregnancy or breast-feeding. breast-feeding.

Caused by human Caused by human immunodeficiency immunodeficiency virus (HIV) virus (HIV) infection infection

Most common routes Most common routes of transmission are of transmission are through sexual through sexual contact, blood, or contact, blood, or from mother to from mother to child during child during pregnancy or pregnancy or breast-feeding. breast-feeding.

Can have infection for years before developing any symptoms of this disease

Can have infection for years before developing any symptoms of this disease

Less common routes of transmission are through accidental needle sticks, artificial insemination, and organ transplants.

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Acquired Immune Acquired Immune Deficiency Syndrome Deficiency Syndrome (AIDS) (AIDS) (cont.)(cont.)

AIDS virus AIDS virus affects the affects the immune system immune system

Counts of CD4 Counts of CD4 cells are used to cells are used to diagnose the diagnose the stage of HIV stage of HIV infection. If infection. If below 200 below 200 patient has AIDS patient has AIDS

AIDS virus AIDS virus affects the affects the immune system immune system

Counts of CD4 Counts of CD4 cells are used to cells are used to diagnose the diagnose the stage of HIV stage of HIV infection. If infection. If below 200 below 200 patient has AIDS patient has AIDS

CD4 cells are types of T cells and are important for the functions of other components of the immune system.

CD4 cells are types of T cells and are important for the functions of other components of the immune system.

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Acquired Immune Acquired Immune Deficiency Syndrome Deficiency Syndrome (AIDS) (AIDS) (cont.)(cont.)

Signs and Symptoms of Signs and Symptoms of AIDS:AIDS:

Low T cell countsLow T cell counts FeverFever Profuse sweatingProfuse sweating WeaknessWeakness Weight lossWeight loss Swollen glandsSwollen glands

Frequent infections

Some rare forms of cancer

A common form of cancer is called “Kaposi’s” sarcoma.

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Allergies Allergies Allergic reaction is Allergic reaction is

an immune an immune response to a response to a substancesubstance

Allergens - trigger Allergens - trigger of allergic of allergic responses responses

Allergic reaction is Allergic reaction is an immune an immune response to a response to a substancesubstance

Allergens - trigger Allergens - trigger of allergic of allergic responses responses

Anaphylaxis - blood vessels dilate quickly causing blood pressure to drop too quickly for organs to adjust. This condition is life threatening.

Anaphylaxis - blood vessels dilate quickly causing blood pressure to drop too quickly for organs to adjust. This condition is life threatening.

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AllergiesAllergies (cont.)(cont.)

Allergic reactions Allergic reactions involve IgE involve IgE antibodies and antibodies and mast cells. mast cells.

IgE antibodies bind to IgE antibodies bind to allergens, they allergens, they cause mast cells cause mast cells to release to release histamine and histamine and heparinheparin

These chemicals trigger allergic reactions.

If a person is receiving allergy shots, he is being injected with tiny amounts of the allergen and reduces symptoms

Immunology in Rheumatic Immunology in Rheumatic DiseasesDiseases

Toll like receptors Toll like receptors (TLRs)(TLRs)

Value of the Immune SystemValue of the Immune SystemMacrophages & toll-like receptors (TLRs)Macrophages & toll-like receptors (TLRs)

10-12 different TLRs can (collectively) bind a wide range of 10-12 different TLRs can (collectively) bind a wide range of pathogenspathogens

EachEach macrophage has all of the set of TLRs macrophage has all of the set of TLRs

Toll-like receptors recognize a variety of PAMPs. Gene duplication of the TLR precursor and divergence of function has led to a family of molecules capable of recognizing different types of pathogen.

TLRs and TLRs and AutoimmunityAutoimmunity

Clear evidence they play a role in SLE Clear evidence they play a role in SLE and RAand RA

Clear evidence that intrinsic Clear evidence that intrinsic molecules trigger TLRs in RA and SLEmolecules trigger TLRs in RA and SLE

Targeted inhibitors of TLRs are in Targeted inhibitors of TLRs are in Phase II trialsPhase II trials

Agonists of TLRs are being used as Agonists of TLRs are being used as vaccine and tumor adjuvantsvaccine and tumor adjuvants

Antigen Presenting CellsAntigen Presenting Cells

Unlike the other cells, TUnlike the other cells, TH H cells only cells only recognize antigen that is recognize antigen that is properly presented with MHC by properly presented with MHC by other cellsother cells

These specialized cells are called These specialized cells are called antigen presenting cells antigen presenting cells

They include macrophages, B They include macrophages, B cells, fibroblasts & dendritic cellscells, fibroblasts & dendritic cells

Major Histocompatibility Major Histocompatibility Complex (MHC)Complex (MHC) Antigen is ingested by the antigen Antigen is ingested by the antigen

presenting cell then presented presenting cell then presented on its surface in molecules called on its surface in molecules called major histocompatibility major histocompatibility complexcomplex

MHC are also the molecules responsible for MHC are also the molecules responsible for rejection in transplant organs rejection in transplant organs

Major Histocompatibility Major Histocompatibility ComplexComplex

MHC proteins MHC proteins =HLA(Human Leucocyte =HLA(Human Leucocyte Antigen) in Antigen) in

humanshumans Molecules on cell surfaces Molecules on cell surfaces

which can display antigen which can display antigen Products of a region of Products of a region of

highly polymorphogenic highly polymorphogenic genes on chromosome 6 genes on chromosome 6

2 types :2 types :

Class I &Class I &

Class IIClass II

Comparison of MHC Class I & II MoleculesComparison of MHC Class I & II Molecules

Class IClass I Class IIClass IIGenesGenes HLA A/B/CHLA A/B/C HLA DHLA D

Expressed on Expressed on All nucleated cellsAll nucleated cells APCs APCs –– B cells, B cells,

macrophages & macrophages &

dendritic cellsdendritic cells

SizeSize 9 to 10 amino acids9 to 10 amino acids

(smaller)(smaller)

12 to 28 amino 12 to 28 amino acidsacids

(larger)(larger)

Source of antigen Source of antigen

displayeddisplayedIntracellular eg viral Intracellular eg viral

infectionsinfectionsExtracellular eg Extracellular eg

bacterial infectionsbacterial infections

Antigen presented Antigen presented to to

CD8+ T cellsCD8+ T cells CD4+ cellsCD4+ cells

( APC = Antigen presenting cell)

Activation of the Adaptive Activation of the Adaptive Immune SystemImmune System Antigens that escape the innate Antigens that escape the innate

immune system encounter the immune system encounter the adaptive system adaptive system

Adaptive immune system Adaptive immune system –– powerful powerful must be activatedmust be activated

Activation of the Adaptive Immune Activation of the Adaptive Immune SystemSystem

1. APC eg Macrophage

ingests Ag

2. Ag presented on cell surface with MHC

3. T cell recognizes its cognate Ag

4. 2nd signal required = protein on APC + a TH cell receptor

5. ACTIVATION&

6. Cytokine production

In this diagram, the macrophage represents the innate system & the TH cell, the adaptive system

CytokinesCytokines

Cells of the immune system communicate Cells of the immune system communicate with each other using cytokineswith each other using cytokines

Protein hormonesProtein hormones Mediate the effect of the innate & Mediate the effect of the innate &

specific immunityspecific immunity Autocrine/ paracrine/endocrineAutocrine/ paracrine/endocrine Effects include cell activation, division, Effects include cell activation, division,

apoptosis, movementapoptosis, movement

Cytokine typesCytokine types Interleukins Interleukins ––

– produced by leucocytes & have effects produced by leucocytes & have effects mainly on WBCmainly on WBC

ChemokinesChemokines ––– chemoattractantschemoattractants

Colony stimulating factorsColony stimulating factors ––– differentiation & proliferation of stem cellsdifferentiation & proliferation of stem cells

InterferonsInterferons ––– interfere with viral replicationinterfere with viral replication

Eg.Eg.Il-2 = a growth factor that stimulates CTLs & Il-2 = a growth factor that stimulates CTLs & NK cells to proliferateNK cells to proliferate

TNF activates primed macrophages & NK cells TNF activates primed macrophages & NK cells

Cells & cytokine productionCells & cytokine production

Cells Cytokines Antigen

IL2TH1 IFN Viruses(CD4) TNF Bacteria

TH0 IL 4

TH2 IL 5 Parasites(CD4) IL10

Cells produce different subgroups of cytokines which will instruct the innate & adaptive systems to produce cells & antibodies against specific antigens.Here is an example

T Cell Subsets – the Family Grows

0 102

103

104

105

< CD45RA>

0

102

103

104

105

< C

CR

7 >

44 28.2

4.7323.1

Naive

CM

EM TEM

Naïve (CD45RA+CCR7+)CM: central memory (CD45RA-CCR7+)EM: effector memory (CD45RA-CCR7-)TEM: terminal effector memory (CD45RA+CCR7-)

IL-12 IL-23

p40p40

p35

IL-12Rβ1

IL-12Rβ1IL-12Rβ2

IL-23R

Signal Signal

p19

Th1 cell proliferation Th17 cell proliferationINF

IL-6IL-1

IL-22

NK or T cellmembrane

2. Tolerance Is2. Tolerance Is…………………………..

the immunologic unresponsiveness the immunologic unresponsiveness to self antigensto self antigens

It allows the immune system to protect the It allows the immune system to protect the body without turning against itself body without turning against itself

The focus is on the adaptive immune systemThe focus is on the adaptive immune system T & B cells must be able to discriminate self T & B cells must be able to discriminate self

from non selffrom non self This occurs centrally & peripherallyThis occurs centrally & peripherally

Central T Cell Central T Cell ToleranceTolerance

T cells are produced T cells are produced in the bone marrow & in the bone marrow & migrate to the migrate to the thymus.thymus.

Here they go through Here they go through a rigorous selections a rigorous selections

process.process. Only T cells that Only T cells that

react to antigen but react to antigen but not self exit.not self exit.

The rest die by The rest die by apoptosis.apoptosis.

NEJM 2001;344(9): 655 – 664.

Peripheral T Cell TolerancePeripheral T Cell Tolerance

If autoreactive T cells enter the circulation,there are several mechanisms that can prevent an autoimmune reaction.

NEJM 2001;344(9): 655 – 664.

B Cell ToleranceB Cell Tolerance

CENTRALCENTRAL–Clonal deletion of autoreactive Clonal deletion of autoreactive B cells in the bone marrow, B cells in the bone marrow, spleen & lymph nodes.spleen & lymph nodes.

PERIPHERALPERIPHERAL–Lack of help from T cells is the Lack of help from T cells is the predominant factor. predominant factor.

Breakdown in peripheral tolerance

3. Autoimmunity3. Autoimmunity

Breakdown in mechanisms preserving Breakdown in mechanisms preserving tolerance to self tolerance to self

Severe enough to cause a pathological Severe enough to cause a pathological condition condition

Autoimmune diseasesAutoimmune diseases

Organ specific e.g.Organ specific e.g.– Insulin dependant diabetesInsulin dependant diabetes– Myasthenia gravisMyasthenia gravis

Multisystem e.g.Multisystem e.g.– Rheumatoid arthritisRheumatoid arthritis– SLESLE

MechanismsMechanisms

GENETIC FACTORSAberant MHC/HLA - present self peptideAutoreactive T & B cells

ENVIRONMENTAL FACTORSInfectious/ noninfectious triggersHypothesis : Molecular mimicry

Molecular mimicry : The antigen looks similar to a self-peptide. As a result, the body produces an immune response to the trigger factor as well as to self.

AUTOIMMUNE DISEASE

The Major Theories in the Development of The Major Theories in the Development of Autoimmune DiseasesAutoimmune Diseases

Release of the normally sequestered antigensRelease of the normally sequestered antigens Increased expression of autoantigen/cryptic Increased expression of autoantigen/cryptic

epitope/MHC IIepitope/MHC II Molecular mimicry, Epitope spreadingMolecular mimicry, Epitope spreading Defects in apoptosisDefects in apoptosis Decreased cell numbers or function of Decreased cell numbers or function of

suppressor and/or regulatory cellssuppressor and/or regulatory cells Altered Th1 and Th2 cytokine patternAltered Th1 and Th2 cytokine pattern Increased expression of costimulatory moleculesIncreased expression of costimulatory molecules Release of inflammatory mediatorsRelease of inflammatory mediators

Autoantibodies in Connective Tissue Autoantibodies in Connective Tissue DiseasesDiseases

Produced by B cellsProduced by B cells May be pathogenic eg.May be pathogenic eg.

– Form immune complexes in lupus Form immune complexes in lupus nephritisnephritis

Markers of certain diseasesMarkers of certain diseases May not be diagnosticMay not be diagnostic

– Apart from rheumatic disorders, they may be Apart from rheumatic disorders, they may be found in normal population & with other found in normal population & with other conditions conditions

– Therefore only test when clinically indicated.Therefore only test when clinically indicated.

Autoantibodies associated with Autoantibodies associated with disease disease

DISEASEDISEASE AUTOANTIBODYAUTOANTIBODY

Rheumatoid ArthritisRheumatoid Arthritis Rheumatoid factorRheumatoid factor

SLESLE ANA,dsDNA, SmithANA,dsDNA, Smith

SclerodermaScleroderma ANA,centromere, ANA,centromere,

topoisomerasetopoisomerase

Antiphospholipid Antiphospholipid

SyndromeSyndromeAnticardiolipin (ACLA)Anticardiolipin (ACLA)

SjogrenSjogren’’s syndromes syndrome Ro, LaRo, La

PolymyositisPolymyositis Jo-1Jo-1

DermatomyositisDermatomyositis Mi-2Mi-2

WegenerWegener’’s s granulomatosisgranulomatosis

c-ANCAc-ANCA

Cellular Targets for autoantibodiesCellular Targets for autoantibodies

Ab to intracellular proteins-proteinase 3•cANCA

Ab to cell membrane Proteins•ACLA

Antinuclear antibodies (ANA)•dsDNA•ENA – Smith, Ro , La, RNP•Centromere, topoisomerase

Ribosomal & lysosomal components-t RNA synthetase• AntiJo 1

Ab to IgG•Rheumatoid factor

This diagram depicts the autoantibodies & their respective target antigens

1. Immune Mechanisms1. Immune Mechanisms2. Tolerance2. Tolerance3. Autoimmunity3. Autoimmunity

4. Rheumatologic conditions4. Rheumatologic conditions– Rheumatoid arthritisRheumatoid arthritis– Systemic Lupus ErythematosisSystemic Lupus Erythematosis– SpondarthropathiesSpondarthropathies– Inflammatory myopathiesInflammatory myopathies– Systemic sclerosisSystemic sclerosis

The above disease will be used to highlight some The above disease will be used to highlight some of the concepts of Immunology in of the concepts of Immunology in Rheumatology.Rheumatology.

Note that the details of each pathway does NOT Note that the details of each pathway does NOT have to be memorized.have to be memorized.

Rheumatoid ArthritisRheumatoid Arthritis

Chronic autoimmune Chronic autoimmune disorderdisorder

Affects 1% of populationAffects 1% of population

A symmetrical peripheral A symmetrical peripheral polyarthritis of unknown polyarthritis of unknown etiology that leads etiology that leads to joint deformity & to joint deformity & destruction due to destruction due to erosion of cartilage & erosion of cartilage & bonebone

Inflammation Drives Inflammation Drives Arthritis Arthritis

The inflammatory process results in damage to The inflammatory process results in damage to cartilage & bonecartilage & bone

NEJM 2001; 344 (12): 907 – 916.

Rheumatoid FactorRheumatoid Factor Rheumatoid Rheumatoid

Factor is an Factor is an autoantibody autoantibody produced in RAproduced in RA

It is however It is however produced in produced in several other several other conditions conditions

Clinical Clinical features are features are important in important in making the making the diagnosisdiagnosis

Anti-CCP AbAnti-CCP Ab

Rheumatoid ArthritisRheumatoid Arthritis Current therapiesCurrent therapies

– Nonsteroidal anti-inflammatory drugs (NSAIDs)Nonsteroidal anti-inflammatory drugs (NSAIDs)– Oral corticosteroidsOral corticosteroids– Disease-modifying antirheumatic drugs (DMARDs)Disease-modifying antirheumatic drugs (DMARDs)

D-penicillamine, auranofin, hydroxychloroquine, D-penicillamine, auranofin, hydroxychloroquine, azathioprine, MTXazathioprine, MTX

MTX has the most rapid onset of action and is well MTX has the most rapid onset of action and is well tolerated with long-term usetolerated with long-term use

Many patients receiving DMARD therapy show only Many patients receiving DMARD therapy show only partial symptom relief and still exhibit features of partial symptom relief and still exhibit features of active diseaseactive disease

New Agents for the New Agents for the Treatment Treatment of RA of RA

Cytokine inhibitorsCytokine inhibitors– Human monoclonal Ab to TNFHuman monoclonal Ab to TNFαα– PEGylated anti-TNFPEGylated anti-TNFαα– Monoclonal antibody to IL-6 receptorMonoclonal antibody to IL-6 receptor– JAK3 inhibitionJAK3 inhibition

Co-stimulatory molecule blockers-abataceptCo-stimulatory molecule blockers-abatacept Targeted B-cell therapy- anti-CD20Targeted B-cell therapy- anti-CD20 yOther unique mechanisms of actionyOther unique mechanisms of action

Systemic Lupus ErythematosusSystemic Lupus Erythematosus

Signs:Signs:ArthritisArthritis““Butterfly” rash on faceButterfly” rash on faceSensitivity to sunlightSensitivity to sunlightRenal failureRenal failureHeadachesHeadachesMental disordersMental disorders

A generalized connective tissue disorder affecting many organs and characterized by the production of many autoantibodies

Systemic lupus erythematosus classification criteria (SOAP BRAIN MD)

1. SSerositis: (a) pleuritis, or (b) pericarditis

2. OOral ulcers3. AArthritis4. PPhotosensitivity

10. MMalar rash11. DDiscoid rash

5. B Blood/Hematologic disorder: (a) hemolytic anemia or(b) leukopenia of < 4.0 x 109 (c) lymphopenia of < 1.5 x

109 (d) thrombocytopenia < 100

X 109

6. RRenal disorder: (a) proteinuria > 0.5 gm/24 h

or 3+ dipstick or(b) cellular casts

7. AAntinuclear antibody (positive ANA) 8. IImmunologic disorders:

(a) raised anti-native DNA antibody binding or(b) anti-Sm antibody or (c) positive anti-phospholipid antibody work-up

9. NNeurological disorder: (a) seizures or (b) psychosis

". ..A person shall be said to have SLE if four or more of the 11 criteria are present, serially or simultaneously, during any interval of observation."

Lupus NephritisLupus Nephritis

The kidney biopsy on the right is from a patient The kidney biopsy on the right is from a patient with diffuse proliferative lupus nephritis shows with diffuse proliferative lupus nephritis shows massive deposits of IgG on immunofluorescencemassive deposits of IgG on immunofluorescence

Ankylosing Ankylosing SpondylitisSpondylitis

AS is a chronic inflammatory disease of the axial skeleton manifested by back pain & progressive stiffness of the spine

Ankylosing Ankylosing SpondylitisSpondylitis

The prevalence of The prevalence of the MHC,HLA-B27 the MHC,HLA-B27 is high in is high in

Caucasians Caucasians

but rare in but rare in Black Black

populations with populations with Ankylosing Ankylosing SpondylitisSpondylitis

DermatomyositisDermatomyositis

An idiopathic inflammatory myopathy associated with certain characteristic cutaneous manifestations

Note: the inflammatory infiltrate in the musclebiopsy of this patient with Dermatomyositis

SclerodermaSclerodermaThe term encompasses a heterogeneous group of conditions linked by the presence of thickenedsclerotic skin lesions

The inflammatory process in Scleroderma results a marked fibrotic precess responsible for many of the clinical features

Scleroderma Lung DiseaseScleroderma Lung Disease

2 important lung diseases which occur due to the inflammatory process in Scleroderma

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SummarySummary

Medical AssistantKnowledge of the immune system forms the basis of understanding many of the diseases and disorders of the immune system and has become the focus of many exciting new treatment strategies.

You must have knowledge of this system when assisting the physician during the examination of a patient who is having problems with their immune system.

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Apply Your Apply Your KnowledgeKnowledge

Your 18-year-old patient Your 18-year-old patient states that he thinks his states that he thinks his right big toe is inflamed. right big toe is inflamed. What symptoms would you What symptoms would you expect to see?expect to see?

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Apply Your KnowledgeApply Your Knowledge - - AnswerAnswer

Redness, heat, swelling, and pain

Your 18-year-old patient states that he thinks his right big toe is inflamed. What symptoms would you expect to see?

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Apply Your Apply Your KnowledgeKnowledge

How can a patient contract HIV?How can a patient contract HIV?

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Apply Your KnowledgeApply Your Knowledge --AnswerAnswer

Most common routes of transmission are through sexual contact, blood, or from mother to child during pregnancy or breast-feeding

How can a patient contract HIV?

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Apply Your Apply Your KnowledgeKnowledge

As you are taking your patient As you are taking your patient to the exam room, you notice to the exam room, you notice that she has “Butterfly” rash that she has “Butterfly” rash on her face. What disorder on her face. What disorder exhibits this sign?exhibits this sign?

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Apply Your KnowledgeApply Your Knowledge --AnswerAnswer

Lupus

As you are taking your patient to the exam room, you notice that she has “Butterfly” rash on her face. What disorder exhibits this sign?

ReferencesReferences

1.1. Sompayrac L. How the Immune System works. Sompayrac L. How the Immune System works. Blackwell Science, Inc. 1999Blackwell Science, Inc. 1999

2.2. Roitt IM. RoittRoitt IM. Roitt’’s Essential Immunology 10s Essential Immunology 10thth ed. ed. Blackwell Science 2001Blackwell Science 2001

3.3. Hochburg et al. Rheumatology 3Hochburg et al. Rheumatology 3rdrd ed. Mosby ed. Mosby 20032003

4.4. UpToDate 12.3UpToDate 12.3

5.5. Kalla AA. Rheumatology Handbook. Rheumatic Kalla AA. Rheumatology Handbook. Rheumatic Diseases Unit Univrersity of Cape Town. Diseases Unit Univrersity of Cape Town. 20032003

References (cont)References (cont)

6.6. Parkin J, Cohen B. An overview of the Parkin J, Cohen B. An overview of the immune system. Lancet 2001;357: 1777-immune system. Lancet 2001;357: 1777-1789.1789.

7.7. Mackay IR, Rosen FS. Tolerance and Mackay IR, Rosen FS. Tolerance and Autoimmunity. NEJM 2001;344(9): 655 Autoimmunity. NEJM 2001;344(9): 655 –– 664. 664.

8.8. Mackay IR, Rosen FS. Autoimmune diseases. Mackay IR, Rosen FS. Autoimmune diseases. NEJM 2001; 345(5): 340-350.NEJM 2001; 345(5): 340-350.

9.9. Epstein FH. Cytokine pathway and Joint Epstein FH. Cytokine pathway and Joint Inflammation in Rheumatoid Arthritis. NEJM Inflammation in Rheumatoid Arthritis. NEJM 2001; 344 (12): 907 2001; 344 (12): 907 –– 916. 916.

10.10. Yuan G et al. Immunologic Intervention in Yuan G et al. Immunologic Intervention in the Pathogenesis of Osteoarthritis. Arthritis & the Pathogenesis of Osteoarthritis. Arthritis & Rheumatism 2003; 48(3) 602- 611.Rheumatism 2003; 48(3) 602- 611.

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